Wu Gan-Bin, Chu Yan-le
Pharmaceutical Department, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450001, China.
Zhongguo Zhong Yao Za Zhi. 2018 Aug;43(15):3192-3197. doi: 10.19540/j.cnki.cjcmm.20180424.001.
To determine the absorption properties and study the intestinal absorption kinetics of poncidin in rats. In situ single pass perfusion model was combined with High Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS/MS) method to investigate the intestinal absorption characteristics and calculate absorption parameters with aspects of drug absorption, concentration and perfusion medium. The absorption of poncidin under acid condition at pH 6.5 was more stable, where intestinal enzymes showed little influence on metabolism, and the absorption was significantly higher than that in pH alkaline condition at pH 8.0 (<0.05). Drug concentrations had no significant influence on absorption rate constant of the same intestinal segment Ka and apparent permeability coefficient Papp values of poncidin. Different concentrations of poncidin showed no significant differences in the Ka and Papp values among duodenum, jejunum and colon, but the values were significantly lower than ileum absorption parameters, with significant differences (<0.05). There was no significant effect of verapamil on intestinal absorption of poncidin. The results showed that poncidin could be absorbed at all the studied intestinal segments while ileum seemed to be the best absorption segment in the concentration range of 10-1 000 μg·L⁻¹. The absorption was characterized by a linear dynamic process of passive transport, without absorption saturation. Weak acid environment was helpful for the intestinal absorption of poncidin, and ponicidin was not a substrate of P-glycoprotein (P-gp).
为测定庞西丁在大鼠体内的吸收特性并研究其肠道吸收动力学。采用原位单向灌流模型结合高效液相色谱 - 质谱联用(HPLC-MS/MS)法,从药物吸收、浓度及灌流介质等方面考察肠道吸收特性并计算吸收参数。庞西丁在pH 6.5的酸性条件下吸收更稳定,此时肠道酶对其代谢影响较小,且吸收显著高于pH 8.0的碱性条件下(<0.05)。药物浓度对庞西丁同一肠段的吸收速率常数Ka及表观渗透系数Papp值无显著影响。不同浓度的庞西丁在十二指肠、空肠和结肠的Ka及Papp值无显著差异,但这些值均显著低于回肠的吸收参数,差异有统计学意义(<0.05)。维拉帕米对庞西丁的肠道吸收无显著影响。结果表明,在10 - 1000μg·L⁻¹浓度范围内,庞西丁在所有研究的肠段均可吸收,其中回肠似乎是最佳吸收肠段。其吸收以被动转运的线性动力学过程为特征,无吸收饱和现象。弱酸环境有助于庞西丁的肠道吸收,且庞西丁不是P-糖蛋白(P-gp)的底物。